New Therapy for Advanced Stage Leukemia After Stem Cell Transplantation

Clinical Study of Granulocyte Colony-stimulating Factor (G-CSF)-Primed, Peripheral-blood Progenitor Cells for the Prevention of Relapse Advanced Stage Leukemia

Hematopoietic stem cell transplantation (HSCT) is one of the best, and sometimes the only, option for the treatment of leukemia, particularly for patients with advanced-stage leukemia. However, relapse rate was still very high for advanced-stage leukemia.

It was found in our previous study that infusion of granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood progenitor cells (GPBPC) instead of non-primed lymphocytes exhibited a comparative or stronger graft-versus-leukemia (GVL) effect and comparative or less incidence of GVHD, rarely being complicated with pancytopenia. When GPBPC infusion was combined with the use of short-term immunosuppressant for GVHD prophylaxis, the incidence of fatal GVHD complicated with GPBPCI was further reduced. Our primary data showed the GPBPCI combined with the use of short-term immunosuppressant was feasible in patients with advanced leukemia to prevent relapse after HLA-mismatched HSCT.

The study hypothesis:

Prevention of relapse using granulocyte colony-stimulating factor-primed peripheral blood progenitor cells following hematopoietic stem cell transplantation in patients with advanced-stage acute leukemia can

• reduce relapse rate
• improve survival

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Procedure: prophylactic GPBPCI

Detailed Description

A G-CSF-primed PBPCI was planned within day 60 post-transplantation before hematologic relapse was diagnosed in patients for which no GVHD occurred or free of GVHD after 2 weeks off immunosuppression for patients receiving GPBPCI after day 90 post HSCT. Before administration of GPBPCI, serious infection had to be cleared and no serious organ failure could be present. The GPBPCI regimen was comprised of G-CSF-primed PBSCs instead of harvested non-primed donor lymphocytes and short-term immunosuppressive agents for prevention of GVHD after GPBPCI. Chimerism status was examined before and after prophylactic treatment with GPBPCI.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital，Institute of Hematology
  • Chongqing, China
    • Xinqiao Hospital，Third Military Medical University
  • Gansu
    • Lanzhou, Gansu, China
      • Lanzhou General Hospital of Lanzhou Command
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital, Southern Medical University
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Soochow University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Medical School of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• high-risk leukemia after HSCT

Exclusion Criteria:

• active GVHD
• early relapse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high-risk leukemia	Procedure: prophylactic GPBPCI; A G-CSF-primed PBPCI was planned within day 60 post-transplantation before hematologic relapse was diagnosed; Other Names: modified DLI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
relapse rate	one year after HSCT

Secondary Outcome Measures

Outcome Measure	Time Frame
survival probability	one year after transplant

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: XiaoJun Huang, M.D., Peking University People's Hospital，Institute of Hematology

Publications and helpful links

General Publications

• Zhou YL, Wu LX, Peter Gale R, Wang ZL, Li JL, Jiang H, Jiang Q, Jiang B, Cao SB, Lou F, Sun Y, Wang CC, Liu YR, Wang Y, Chang YJ, Xu LP, Zhang XH, Liu KY, Ruan GR, Huang XJ. Mutation topography and risk stratification for de novo acute myeloid leukaemia with normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). Br J Haematol. 2020 Jul;190(2):274-283. doi: 10.1111/bjh.16526. Epub 2020 Feb 26.
• Yan CH, Liu QF, Wu DP, Zhang X, Xu LP, Zhang XH, Wang Y, Huang H, Bai H, Huang F, Ma X, Huang XJ. Prophylactic Donor Lymphocyte Infusion (DLI) Followed by Minimal Residual Disease and Graft-versus-Host Disease-Guided Multiple DLIs Could Improve Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Refractory/Relapsed Acute Leukemia. Biol Blood Marrow Transplant. 2017 Aug;23(8):1311-1319. doi: 10.1016/j.bbmt.2017.04.028. Epub 2017 May 5. Erratum In: Biol Blood Marrow Transplant. 2020 Jan;26(1):214.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: October 12, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (Estimate): October 19, 2011

Study Record Updates

• Last Update Posted (Estimate): April 7, 2015
• Last Update Submitted That Met QC Criteria: April 5, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: PUPH IRB [2010] (78)